Pharmaceutical composition for improving reproductive function

Abstract

The invention discloses a pharmaceutical composition for improving reproductive function, and belongs to the field of traditional Chinese medicines. The rhizoma polygonati polysaccharide and the royal jelly are combined for use to play a synergistic effect, so that the composition has a good effect on improving the reproductive function and the ovarian reserve function, particularly has a good effect on the reproductive function of old mice, and has obvious advantages and characteristics compared with independent application of the rhizoma polygonati polysaccharide and the royal jelly; the rhizoma polygonati polysaccharide and the royal jelly can be used as a medicine for improving the reproductive function and the ovarian reserve function as a medicine composition.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine, and particularly relates to a pharmaceutical composition for improving reproductive function. Background Art

[0002] Infertility includes primary infertility and secondary infertility. Primary infertility was called "total infertility" or "childlessness" in ancient times, while secondary infertility was called "broken fertility" in ancient times. The causes of infertility are complex and diverse, among which ovulatory dysfunction is one of the important causes. The normal growth and development of follicles and ovulation depend on the normal function of ovarian function. If a woman's ovarian function is abnormal, it will lead to infertility.

[0003] The potential of the ovaries to produce eggs in quantity and quality is called ovarian reserve (OR) function, which is closely related to the size of the primordial follicle pool in the ovaries and determines the reproductive lifespan of female individuals. Decreasing ovarian reserve (DOR) is prone to develop into premature ovarian failure (POF), which has become a common cause of female infertility. POF causes amenorrhea before the age of 40, with or without perimenopausal syndrome, increased gonadotropin levels, and decreased estrogen levels. In recent years, the number of infertility patients caused by premature ovarian function decline has increased year by year, seriously affecting women's reproductive health and quality of life. At present, assisted reproductive technology (ART) or hormone replacement therapy (HRT) are mainly used to solve patients' fertility problems and supplement hormones.

[0004] HRT mainly supplements exogenous hormones to make up for the lack of hormone secretion in the original body, so as to improve the endocrine status of perimenopausal women and delay aging. Although HRT treatment has significant short-term efficacy, it is often easy to relapse after discontinuation of the drug, and its adverse reactions cannot be ignored. Some studies have reported that HRT may increase the risk of gynecological tumors such as breast cancer and ovarian cancer, and is subject to certain restrictions in clinical application. Therefore, it is necessary to research and develop safer and more effective natural substitutes with HRT effects. Traditional Chinese medicine has a history of more than 5,000 years in my country. It has the unique advantages of multiple targets, multiple active ingredients, overall regulation and few adverse reactions. Among them, the treatment of POF with kidney-tonifying method as the core has achieved good results in clinical practice, showing broad application prospects. .

[0005] "Huangjing" was first recorded in Shennong's Herbal Classic. It is a perennial herbaceous plant of the genus Polygonatum in the Liliaceae family, mainly distributed in the northern temperate zone and northern subtropical zone. The 2020 edition of the Chinese Pharmacopoeia records that Huangjing is the dried rhizome of Polygonatum kingianum Coll. Et Hemsl., Polygonatum sibiricum Red. or Polygonatum cyrtonema Hua; sweet and flat; enters the spleen, lung and kidney meridians; has the effects of replenishing qi and nourishing yin, strengthening the spleen, moistening the lungs and benefiting the kidneys; used for spleen and stomach qi deficiency, fatigue, insufficient stomach yin, dry mouth and poor appetite, dry cough due to lung deficiency, cough due to fatigue and hemoptysis, insufficient essence and blood, soreness of waist and knees, etc., and shows potential medicinal value in anti-aging, regulating immunity, lowering blood sugar and regulating blood lipids. Polygonatum contains a variety of active ingredients, including polysaccharides, terpenes, alkaloids, flavonoids, sterols and volatile oils, among which polysaccharides have the highest content in Polygonatum, and are also the main basis for evaluating the quality of Polygonatum. The molecular weight of polysaccharides isolated from Polygonatum is mainly distributed in the range of 2.2 to 360 kDa, including fructans and heteropolysaccharides composed of monosaccharides such as glucose, mannose, galactose, galacturonic acid, glucuronic acid, rhamnose, arabinose or xylose; Polygonatum is mainly used in health foods to enhance immunity, assist in lowering blood sugar, assist in lowering blood lipids, regulate intestinal flora, delay aging and anti-oxidation.

[0006] Royal jelly, also known as royal jelly, royal jelly, royal jelly, and bee jelly, is the secretion of the pharyngeal glands of young worker bees that cultivate larvae in the beehive. It is the food for the larvae that will become queen bees and the lifelong food of queen bees. The main components of royal jelly: protein accounts for 50% of the dry weight, of which 2 / 3 are albumin and 1 / 3 are globulin. Amino acids account for about 0.8% of the dry weight in royal jelly. The 10 essential amino acids for the human body are all present in royal jelly. Royal jelly contains acid and rich vitamins, especially B vitamins. It has the effects of lowering blood lipids, preventing arteriosclerosis, and lowering blood sugar; helping the body resist diseases; strengthening the autonomic nervous center, restoring gastrointestinal function, and containing 10-HDH, which has a bactericidal effect. It has auxiliary therapeutic effects on gastric ulcers, chronic gastritis, hepatitis, and arthritis.

[0007] However, in the prior art, there is no report on the effect of the combination of polygonatum polysaccharide and royal jelly on reproductive function. Summary of the invention

[0008] Based on the deficiencies in the prior art, the present invention provides an application of polygonatum polysaccharide and royal jelly in combination for improving reproductive function. The combination of the two exerts a synergistic effect and has a good effect on improving reproductive function.

[0009] The technical solution of the present invention is as follows:

[0010] The invention provides the use of polygonatum polysaccharide and royal jelly as a pharmaceutical composition in the preparation of a drug for improving reproductive function.

[0011] The mass ratio of polygonatum polysaccharide to royal jelly is 1000:1-2000; preferably, the mass ratio of polygonatum polysaccharide to royal jelly is 10:1-100.

[0012] Most preferably, the mass ratio of polygonatum polysaccharide to royal jelly is 1:1.

[0013] The dosage form of the pharmaceutical composition is liquid injection, powder injection, tablet, capsule, powder, pill, oral liquid, paste, granule or dressing. When the pharmaceutical composition is an oral liquid, the dosage of the oral pharmaceutical composition is 13.3 g per person per day. In the embodiment of the present invention, the dosage of the pharmaceutical composition administered to mice by gavage is 2000 mg / kg, which is equivalent to 13.3 g per person per day.

[0014] Preferably, the subject for improving reproductive function is a woman with low reproductive function, wherein the low reproductive function is manifested in increased serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, decreased serum estradiol (E2) and anti-Mullerian hormone (AMH) levels, decreased ovarian and uterine organ indexes, the number of ovarian primordial follicles, the number of secondary follicles and the number of antral follicles, and an increase in the number of ovarian atretic follicles.

[0015] The improvement of reproductive function in the present invention is manifested in that it can increase the pregnancy rate and litter size of mice, improve the ovarian and uterine organ indexes, increase the number of ovarian primordial follicles, the number of secondary follicles and the number of antral follicles, and reduce the number of ovarian atretic follicles, and have a significant improvement effect on FSH, LH, E2 and AMH levels.

[0016] The present invention also provides a pharmaceutical composition for improving reproductive function, wherein the active ingredients include polygonatum polysaccharide and royal jelly.

[0017] The mass ratio of polygonatum polysaccharide to royal jelly is 1000:1-2000; preferably, the mass ratio of polygonatum polysaccharide to royal jelly is 10:1-100.

[0018] Most preferably, the mass ratio of polygonatum polysaccharide to royal jelly is 1:1.

[0019] The active ingredients of the present invention can be commercially available products, or can be prepared by extracting raw medicinal materials according to conventional methods. The pharmaceutical composition of the present invention can be prepared into liquid injection, powder injection, tablet, capsule, powder, pill, oral liquid, paste, granule or dressing after adding various conventional pharmaceutical excipients required for preparing different dosage forms. When the pharmaceutical composition is an oral liquid, the dosage of the oral pharmaceutical composition is 13.3g per person per day. In the embodiment of the present invention, the dosage of the pharmaceutical composition given to mice by gavage is 2000mg / kg, which is equivalent to 13.3g per person per day.

[0020] Beneficial effects of the present invention:

[0021] The present invention combines polygonatum polysaccharide with royal jelly to exert a synergistic effect, has a good effect on improving reproductive function, especially has a good effect on improving the reproductive function of elderly mice, has obvious advantages and characteristics compared with the use of polygonatum polysaccharide and royal jelly alone, and polygonatum polysaccharide and royal jelly as a pharmaceutical composition can be used as a drug for improving reproductive function. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The effects of different ratios of polygonatum polysaccharide and royal jelly on the ovary and uterine organs of mice; A: polygonatum polysaccharide group; B: royal jelly group; C: HF (10:1) combination group; D: HF (1:1) combination group; E: HF (1:10) combination group; F: elderly mouse control group.

[0023] Figure 2 The effects of different ratios of polygonatum polysaccharide and royal jelly on the development of ovarian follicles in mice; A: polygonatum polysaccharide group; B: royal jelly group; C: HF (10:1) combination group; D: HF (1:1) combination group; E: HF (1:10) combination group; F: elderly mouse control group; the magnification is 100 times. DETAILED DESCRIPTION

[0024] The beneficial effects of the drug of the invention are further described below through experimental examples, which include the effects of the composition of the invention on the reproductive function, ovarian reserve function, etc. of old mice and young mice.

[0025] Example 1

[0026] Take 2000g of fresh and dried Polygonatum cyrtonema, crush it, boil it with 10 times the amount of water for three times, each time for 1.5 hours, filter the decoction, combine the filtrate and concentrate it, add anhydrous ethanol to 80% ethanol precipitation, filter it, remove the protein, and air-dry it naturally to obtain Polygonatum cyrtonema polysaccharide.

[0027] Take 500g of fresh royal jelly, freeze-dry it, and make it into dry powder to obtain royal jelly powder.

[0028] In parts by weight, 400 parts of polygonatum polysaccharide and 40 parts of royal jelly are mixed to obtain a pharmaceutical composition, hereinafter referred to as HF (10:1) composition. 400 parts of polygonatum polysaccharide and 400 parts of royal jelly are mixed to obtain a pharmaceutical composition, hereinafter referred to as HF (1:1) composition. 400 parts of polygonatum polysaccharide and 400 parts of royal jelly are mixed to obtain a pharmaceutical composition, hereinafter referred to as HF (1:10) composition.

[0029] This example is only an illustrative description of the preparation method of polygonatum polysaccharide and royal jelly, and does not constitute a limitation of the present invention. The above two active components have respectively recognized preparation methods and marketed products in the prior art, and can be applied to the present invention to achieve the same therapeutic effect as the above HF composition.

[0030] Example 2: Effect of the pharmaceutical composition on reproductive function of female aged mice:

[0031] SPF female ICR aged mice aged 8-10 months were randomly divided into the following groups according to their body weight: aged mice control group (water 20 ml / kg), Polygonatum sibiricum polysaccharide group (1000 mg / kg), Royal jelly group (1000 mg / kg), HF (10:1) combination group (2000 mg / kg), HF (1:1) combination group (2000 mg / kg) and HF (1:10) combination group (2000 mg / kg), 8 mice in each group, and the corresponding test substances were gavaged daily for 18 consecutive days. Starting from the 13th day, 3 female mice were paired with 1 male mouse in a cage for a total of 10 days, and the pregnancy rate of mice and the number of offspring after pregnancy were observed. The results are shown in Table 1.

[0032] Table 1 Effects of HF composition on pregnancy rate and litter size in aged mice ( , n=8)

[0033] Group Weight before (g) Weight after (g) Pregnancy rate (%) Number of litters Polygonatum cyrtonema polysaccharide group 44.4±2.58 47.4±1.59* 50.0 9.5±1.29* Royal Jelly Group 44.9±3.07 46.7±2.44 62.5 7.2±0.84 HF (10:1) composition 44.1±2.39 47.5±2.26 62.5 8.4±1.52** HF (1:1) composition 44.3±3.66 48.3±3.12* 62.5 10.6±2.07*** HF (1:10) composition 44.7±2.83 47.1±2.51 50.0 8.8±0.96** Elderly rat control group 44.0±2.91 45.2±2.23 37.5 7.0±1.00

[0034] Note: *, **, *** indicate P < 0.05, 0.01, 0.001 compared with the aged rat control group.

[0035] As shown in Table 1, oral administration of polygonatum polysaccharide, royal jelly and HF combination to elderly mice had a certain effect on increasing the weight of mice, among which the polygonatum polysaccharide group and HF (1:1) combination had the best effect, which was significantly different from the control group (P < 0.05); oral administration of polygonatum polysaccharide, royal jelly and HF combination to elderly mice had a promoting effect on the pregnancy rate and litter size of mice, among which the polygonatum polysaccharide group and each HF combination had a significant difference from the control group (P < 0.05 ~ 0.001); at the same time, the results showed that the HF combination had a better effect on improving the weight, pregnancy rate and litter size of mice than the use of polygonatum polysaccharide and royal jelly alone, and the HF (1:1) combination had the best effect among the HF combinations.

[0036] Example 3: Effects of the drug composition on the ovarian and uterine organ indexes of female aged mice

[0037] SPF female ICR aged mice aged 8-10 months were randomly divided into the following groups according to their body weight: aged mice control group (water 20 ml / kg), Polygonatum sibiricum polysaccharide group (1000 mg / kg), Royal jelly group (1000 mg / kg), HF (10:1) combination group (2000 mg / kg), HF (1:1) combination group (2000 mg / kg) and HF (1:10) combination group (2000 mg / kg), 8 mice in each group, and the corresponding test substances were gavaged daily for 10 consecutive days. From the day after the last gavage, the estrous cycle of mice was observed by vaginal exfoliated cell smear method, mice in the estrus period (vaginal exfoliated cell smear containing a large number of white blood cells and a small number of epithelial cells and mucosa) were taken, anesthetized with 2% sodium pentobarbital, blood was taken to separate serum, and after the mice were killed, the bilateral ovaries and uterus were taken, photographed, weighed and the organ index was calculated. The results are shown in Table 2. Figure 1 .

[0038] Table 2 Effects of HF composition on the organ indexes of mouse ovary and uterus ( n=8)

[0039] Group Initial body weight (g) Final body weight (g) Ovarian index (g / 100g) Uterine index (g / 100g) Polygonatum cyrtonema polysaccharide group 44.4±2.23 47.1±3.11 0.073±0.010 0.400±0.058 Royal Jelly Group 44.2±2.03 46.8±2.50 0.068±0.013 0.394±0.038 HF (10:1) composition 44.1±2.17 47.0±2.45 0.072±0.015 0.394±0.041 HF (1:1) composition 44.4±3.81 47.4±2.60 0.078±0.013 0.412±0.147 HF (1::10) composition 43.5±2.59 46.0±2.21 0.069±0.007 0.393±0.037 Elderly rat control group 43.7±2.87 44.9±2.71 0.065±0.014 0.399±0.045

[0040] From Table 2, Figure 1 It can be seen that oral administration of Polygonatum sibiricum polysaccharide, royal jelly and various HF compositions to elderly mice had a certain effect on increasing the weight of mice, among which the HF (1:1) composition had the best effect, but there was no significant difference compared with the elderly mouse control group (P>0.05); oral administration of Polygonatum sibiricum polysaccharide, royal jelly and various HF compositions to elderly mice had a certain effect on improving the ovarian and uterine organ indexes, among which the HF (1:1) composition had the best effect, but there was no significant difference compared with the elderly mouse control group (P>0.05).

[0041] Example 4: Effects of the drug composition on ovarian histology and follicle count in female aged mice

[0042] SPF female ICR aged 8-10 months were randomly divided into: aged mouse control group (water 20 ml / kg), Polygonatum sibiricum polysaccharide group (1000 mg / kg), royal jelly group (1000 mg / kg), HF (10:1) combination group (2000 mg / kg), HF (1:1) combination group (2000 mg / kg) and HF (1:10) combination group (2000 mg / kg), 8 mice in each group, and the corresponding test substances were gavaged daily for 10 consecutive days. Starting from the day after the last oral gavage, the estrous cycle of mice was observed using the vaginal exfoliated cell smear method. Mice in the diestrus period (vaginal exfoliated cell smears contained a large number of leukocytes and a small number of epithelial cells and mucosa) were taken and anesthetized with 2% sodium pentobarbital. Blood was taken to separate serum. After the mice were killed, the ovaries were taken for HE staining, and the follicles of each developmental stage in the whole field of view of the ovarian sections were detected and counted. The criteria for judging the follicles at each level are as follows: ① Primordial follicles: including primordial follicles and primary follicles. Primordial follicles are composed of a single layer of flat granulosa cells surrounding a central oocyte. Primary follicles: a single layer of cuboidal granulosa cells surrounding a central oocyte, or a single layer of flat granulosa cells containing at least 3 cuboidal epithelial cells; ② Secondary follicles: at least 2 layers of granulosa cells surround the oocyte, and no antral cavity is formed; ③ Antral follicles: at least 2 layers of granulosa cells surround the oocyte, and the antral cavity can be seen in the follicle; ④ Atretic follicles: the follicle wall is concave inward, the oocyte is irregular in shape, the zona pellucida collapses, the oocyte nucleus is condensed, fragmented, and dissolved, and the surrounding granulosa cells are atrophied, loose, and even fall off into the antral cavity. The results are shown in Table 3. Figure 2 .

[0043] Table 3 Effects of HF composition on the number of ovarian follicles in female aged mice ( n=8)

[0044] Group Primordial follicle Secondary follicles Antral follicle Atretic follicle Polygonatum cyrtonema polysaccharide group 29.9±4.26 26.4±5.99 23.1±5.44 39.7±4.84* Royal Jelly Group 30.1±6.07 27.4±3.89 22.9±6.16 40.2±4.20* HF (10:1) composition 30.3±5.59 26.9±6.62 23.9±5.19 36.1±6.51** HF (1:1) composition 32.9±5.44* 30.6±4.64* 26.4±6.75 34.6±6.75** HF (1::10) composition 30.9±6.02 27.0±5.76 23.4±4.98 37.1±7.78* Elderly rat control group 26.5±4.51 24.2±5.22 21.0±3.56 45.4±5.31

[0045] Note: *, ** indicate P < 0.05, 0.01 compared with the aged rat control group.

[0046] From Table 3, Figure 2It can be seen that oral administration of Polygonatum sibiricum polysaccharide, royal jelly and various HF compositions to aged mice had a significant increasing effect on the number of primordial follicles, secondary follicles and antral follicles in the mouse ovaries, among which the HF (1:1) composition had the most significant effect on the number of primordial follicles and secondary follicles in the mouse ovaries, and there was a significant difference compared with the aged mouse control group (P < 0.05); oral administration of Polygonatum sibiricum polysaccharide, royal jelly and various HF compositions to aged mice had a significant decreasing effect on the number of atretic follicles in the mouse ovaries, and there was a significant difference compared with the aged mouse control group (P < 0.05-0.01). At the same time, the results showed that the various HF compositions were better than Polygonatum sibiricum polysaccharide and royal jelly alone in increasing the number of primordial follicles, secondary follicles and antral follicles in the ovaries and decreasing the number of atretic follicles in the ovaries, and the HF (1:1) composition had the best effect among the HF compositions.

[0047] Example 5: Effect of the pharmaceutical composition on the levels of serum sex hormones FSH, LH, E2, and AMH in female aged mice

[0048] SPF female ICR aged 8-10 months were selected and randomly divided into: aged mouse control group (water 20 ml / kg), Polygonatum sibiricum polysaccharide group (1000 mg / kg), royal jelly group (1000 mg / kg), HF (10:1) combination group (2000 mg / kg), HF (1:1) combination group (2000 mg / kg) and HF (1:10) combination group (2000 mg / kg), with 8 mice in each group. At the same time, 3-month-old young mice were set as controls. Each group of mice was gavaged with the corresponding test substance every day for 10 consecutive days. Starting from the day after the last oral administration, the estrous cycle of mice was observed by vaginal exfoliated cell smear method. Mice in the estrus period (vaginal exfoliated cell smear contained a large number of leukocytes and a small number of epithelial cells and mucosa) were taken and anesthetized with 2% sodium pentobarbital. Blood was collected to separate serum. ELISA kits were used to detect the levels of mouse serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and anti-Mullerian hormone (AMH). The results are shown in Table 4.

[0049] Table 4 Effects of HF composition on serum sex hormones FSH, LH, E2, and AMH levels in mice ( n=8)

[0050] Group FSH (mIU / ml) LH (mIU / ml) E2 (pg / ml) AMH (ng / ml) Polygonatum cyrtonema polysaccharide group 2.871±0.475 1.536±0.095 37.881±2.394 0.212±0.032* Royal Jelly Group 2.833±0.433 1.531±0.139 36.531±2.430 0.203±0.024 HF (10:1) composition 2.762±0.407 1.522±0.102 35.635±2.990 0.210±0.029* HF (1:1) composition 2.597±0.252* 1.516±0.111 38.786±1.270 0.220±0.036* HF (1:10) composition 2.817±0.449 1.518±0.104 37.954±2.610 0.189±0.031 Elderly rat control group <![CDATA[3.081±0.533 Δ ]]> 1.561±0.085 36.708±2.987 <![CDATA[0.176±0.034 Δ ]]> Young rat control group 2.340±0.503 1.484±0.077 39.202±3.267 0.232±0.046

[0051] Note: * indicates P < 0.05 compared with the elderly rat control group; Δ Compared with the young rat control group, P < 0.05.

[0052] As shown in Table 4, compared with young mice, the serum FSH and LH levels of old mice tended to increase, while the serum E2 and AMH levels tended to decrease. The serum FSH and AMH levels of old mice were significantly different from those of the young mice control group (P < 0.05), indicating that the old mice had ovarian dysfunction. Gavage of Polygonatum sibiricum polysaccharide, royal jelly and various HF compositions to old mice had a decreasing effect on serum FSH and LH levels, and an increasing effect on serum E2 and AMH levels. Among them, the HF (1:1) composition had the most significant effect on decreasing serum FSH, and there was a significant difference compared with the old mice control group (P < 0.05). Polygonatum sibiricum polysaccharide, HF (10:1) composition and HF (1:1) composition had a significant increasing effect on AMH content, and there was a significant difference compared with the old mice control group (P < 0.05).

[0053] Serum sex hormone levels are closely related to ovarian function. An increase in FSH at any age, accompanied by an increase in LH levels and a decrease in E2 levels, means ovarian dysfunction. The change in AMH concentration is consistent with the trend of ovarian aging and is not affected by the menstrual cycle. It is an important indicator for evaluating ovarian reserve function. Intragastric administration of Polygonatum sibiricum polysaccharide, royal jelly and various HF compositions significantly improved the levels of serum sex hormones FSH, LH, E2 and AMH. Among them, the HF (1:1) composition had the best effect and significantly improved the ovarian reserve function.

[0054] From the above experiments, it can be seen that the HF composition of the present invention has a good effect on the reproductive function and ovarian reserve function of old mice and young mice, and has obvious advantages and characteristics compared with the use of polygonatum polysaccharide and royal jelly alone. The HF composition can be used as a drug to improve reproductive function and ovarian reserve function.

Claims

1. Application of polygonatum polysaccharide and royal jelly as a pharmaceutical composition in the preparation of drugs for improving reproductive function.

2. The use according to claim 1, characterized in that: The mass ratio of polygonatum polysaccharide to royal jelly is 1000:1-2000; most preferably, the mass ratio of polygonatum polysaccharide to royal jelly is 10:1-100.

3. The use according to claim 2, characterized in that: The mass ratio of polygonatum polysaccharide to royal jelly is 1:

1.

4. The use according to claim 1, characterized in that: The dosage form of the pharmaceutical composition is liquid injection, powder injection, tablet, capsule, powder, pill, oral liquid, paste, granule or dressing.

5. The use according to claim 4, characterized in that: When the pharmaceutical composition is an oral liquid, the dosage of the oral pharmaceutical composition is 13.3 g per person per day.

6. The use according to claim 1, characterized in that: The subjects for improving reproductive function are women with low reproductive function.

7. A pharmaceutical composition for improving reproductive function, characterized in that: Active ingredients include Polygonatum sibiricum Polysaccharide and Royal Jelly.

8. The pharmaceutical composition according to claim 7, characterized in that The mass ratio of polygonatum polysaccharide to royal jelly is 1000:1-2000; The mass ratio of polygonatum polysaccharide to royal jelly is 10:1-100; The mass ratio of polygonatum polysaccharide to royal jelly is 1:

1.

9. The pharmaceutical composition according to claim 7, characterized in that The dosage form of the pharmaceutical composition is liquid injection, powder injection, tablet, capsule, powder, pill, oral liquid, paste, granule or dressing.

10. The pharmaceutical composition according to claim 9, characterized in that When the pharmaceutical composition is an oral liquid, the dosage of the oral pharmaceutical composition is 13.3 g per person per day.

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